Hu H, Shao M & Li ZW (1999). Enhancement of GABA-activated current by muscarine in rat dorsal root ganglion neurons. Neuroscience 89(3): 883-890. PMID: 10199621


The modulation of GABA-gated ion channel responses to GABA, pentobarbital and diazepam by muscarine was studied in freshly isolated ratdorsal root ganglion neurons using a whole-cell patch-clamp technique. Muscarine enhanced current activated by 5 microM GABA dose-dependently with an EC50 of 40 +/- 2 microM. This potentiation was not blocked by pirenzepine, gallamine and atropine, the specific and non-specific muscarinic receptor antagonists. Muscarine shifted the GABA dose-response curve to the left, with the GABA EC50 decreased from 45 +/- 2 to 13 +/- 2 microM. The maximal response to GABA was suppressed to 89.3 +/- 4.6% as compared with the control (100%) by 80 microMmuscarine. Muscarine potentiated GABA (1-100 microM)-activated current in a voltage-independent manner. Muscarine shifted the dose-response curve for pentobarbital enhancement of GABA-activated current to the left, and the enhancement of GABA-activated current by muscarine was additive to that of pentobarbital over all pentobarbital concentrations. Muscarine shifted the dose-response curve for diazepam (1-100 nM)enhancement of GABA-activated current to the left. However, muscarine attenuated the facilitatory effect of saturating concentrations of diazepam (> 100 nM). The potentiating effect of muscarine was blocked by 1 nM ethyl-beta-carboline-3-carboxylate, the inverse agonist of benzodiazepine receptors. These results suggest that GABA-gated ion channel responses to GABA and pentobarbital were potentiated by muscarine and the binding site(s) for muscarine might be related to those for diazepam.

 Hongzhen Hu  Hu Lab  PubMed